Plasma thyrotropin levels were measured after the acute i.v. administration of 400 µg of synthetic thyrotropin-releasing hormone (TRH) in 6 patients with Addison’s disease, 2 patients with thrombo-cytopenia, and 3 postmenopausal women before and after treatment with cortisone acetate (37.5 mg/day), prednisone (150 mg/day) and diethylstilbesterol (15.0 mg), respectively. All had normal thyroid function with the exception of one hypothyroid postmenopausal woman. There was no significant difference between the responses to TRH before and after steroids, nor between either response and the TSH release found in a group of 20 healthy male volunteers, except for the hypothyroid woman who had a supranormal response and the thrombocytopenic patients whose responses were blunted. In addition, 5 normal volunteers received 100 µg TRH i.v. 1 h after the acute i.v. administration of 30.0 mg methyl prednisolone, 3.0 mg ethinyl estradiol, or saline. There was no significant change in the basal TSH concentration during the 1-hour interval prior to TRH treatment, and the TSH response to TRH after the administration of either steroid was not significantly different from that after the saline control. It is concluded that neither acute pharmacologic treatment nor chronic replacement therapy with either estrogens or corticosteroids affects the TSH response of the pituitary to TRH in man. However, chronic pharmacologic treatment with glucocortico-steroids may have a suppressive effect.